This invention relates to a novel process for preparing optically active 2-oxoimidazolidine derivatives useful as pharmaceutical compounds.
This invention also relates to a novel intermediate of said 2-oxoimidazolidine derivative.
2-Oxoimidazolidine derivatives represented by the formula: ##STR3## wherein R.sup.1 represents hydrogen atom or a lower alkyl group and * represents an asymmetric carbon atom, are pharmaceutical compounds useful as hypotensors having excellent angiotensin converting enzyme (ACE) inhibitory activity.
The 2-oxoimidazolidine derivatives have three asymmetric carbons within the molecule, and their absolute configurations affect greatly the activity, and it has been known in the art that compounds of (S, S, S) configuration in which the absolute configurations of the three asymmetric carbon atoms are all (S) configurations are most preferred (Japanese Patent Publication No. 58233/1985).
As a process for preparing compounds having such (S, S, S) configuration, in the above-mentioned patent specification, there is disclosed a process which comprises (1) reacting a (4S)-1-methyl-2-oxoimidazolidine-4-carboxylic acid ester with 2-bromopropionic acid chloride to form (4S)-1-methyl-3-(2-bromopropionyl)-2-oxoimidazolidine-4-carboxylic acid ester, (2) reacting this product with a (2S)-2-amino-4-phenylbutyric acid ester, then separating the compound of (S, S, S) configuration from the product, and subsequently (3) eliminating the ester residue.
However, according to the above known method, in the condensation reaction of the step (2), the compound of (S, S, S) configuration and the compound of (S, R, S) configuration are formed, and also diastereo-selectivity is exhibited to give the compound of (S, R, S) configuration as the major product. For this reason, there have been involved drawbacks that separation of the compound of (S, S, S) configuration from the compound of (S, R, S) configuration is required for isolation thereof and also that the isolation yield of the (S, S, S) isomer is low.
Also, in the above known method, even when 2-bromopropionic acid chloride may be replaced with a compound of (S) configuration or (R) configuration, racemization and diasteroselectivity occur in the reaction of the step (2) to produce compounds of (S, S, S) configuration and (S, R, S) configuration, and also give the compound of (S, R, S) configuration as the major product, thus involving the same drawbacks as mentioned above.